The GPLA complex is the major histocompatibility complex of the guinea pig, and thus determines two sets of cell surface glycoproteins which occupy a central role in the immunogenetic phenomena which have been observed in this species. The two sets of glycoproteins are the classic histocompatibility antigens, the GPLA-B and -S antigens, and the Ia antigens. This research application proposes to continue a chemical and structural characterization of the Ia antigens with the aim of achieving an understanding of how the structure of these antigens allows them to subserve their function. Antigens will be internally radiolabeled with a 3H-amino acid or 3H-fucose, solubilized by the non-ionic detergent NP-40, purified by lentil lectin or ricin lectin affinity chromatography, isolated by immunoprecipitation, and examined by electrophoresis, peptide mapping, and amino acid sequencing. Ia molecules from strain 2, strain 13, and strain B/lac will be compared by peptide mapping studies and partial N-terminal amino acid sequencing in an effort to assign alleles at Ia loci. The alpha and beta chains of Ia.3,5 will be sequenced as completely as possible. Differences will be sought between Ia molecules derived from different subpopulations of immunocompetent cells. A 98,000 d macrophage molecule reactive with some anti-Ia antisera will be characterized. The carbohydrate moieties of the Ia molecules will be further characterized. Guinea pig T cell-mouse thymoma interspecies hybrids will be studied to chemically characterize a putative T cell receptor for Ia antigens using specific xenoantisera, 2 dimensional gel electrophoresis, tryptic peptide mapping, and partial N-terminal amino acid sequencing.